SUMMARY/ABSTRACT: Here we seek to understand the evolution of resistance to pyrethroid insecticides in Aedes aegypti, an important vector of human diseases such as dengue and Zika. Pyrethroid insecticides are widely used for control of adult Aedes, but resistance has evolved in many populations, representing global challenge for control of this vector and the diseases it transmits. Finding strategies for delaying the development of resistance by mosquito vectors to the few available insecticides is critical. To do so, it is essential to identify the level of resistance conferred, by common resistance alleles, to insecticides that target the voltage sensitive sodium channel (VSSC). This information will fill a critical data gap in our understanding of the evolution of resistance and will inform what options exist in populations where the different resistance alleles are found. Our long-term goals are to understand the importance of different Vssc alleles in the evolution of resistance so that this important process can be understood and the development of resistance can be delayed. Our short-term goal is to measure the level of resistance conferred by different Vssc mutations found in populations across the globe. To accomplish this goal we will pursue two specific aims. Aim 1. Isolate seven congenic (to the susceptible Liverpool strain) strains that have one of the common unstudied Vssc resistance alleles. Aim 2. Determine the level of resistance conferred by each Vssc allele to twenty insecticides that target the VSSC. This proposal fills an important data gap in our understanding of insecticide resistance in A. aegypti by quantitating the phenotype that the different alleles confer. In addition, our results will demonstrate what cross-resistance spectrum is conferred by each allele. This information will provide us with a vastly improved understanding of pyrethroid resistance in A. aegypti, and yield key information for resistance management in this important vector of human disease.